The proposal seeks acquisition of a TOF mass spectrometer coupled with an HPLC for accurate mass determination of small molecules such as natural products, organometallic compounds, nucleic acids and non-polar organic synthetic intermediates that are generated in the research groups of six major NIH-supported research groups at three departments of University of California, San Diego. The HPLC-TOF will be used for determination of composition and formulas of novel natural products obtained from marine bacteria and invertebrates, characterize enzyme-catalyzed reactions of genetically-engineered polyketide synthase complexes, nucleic acids prepared with modified base and sugar components, organometallic compounds for novel carbon-carbon bond formation or for transformations of simple thermodynamically stable molecules such as CO2 and NO2. The separations capability of the LC component will allow measurements of very minor components of moderately complex fractionated natural product extracts, and 'real-time'monitoring of reaction pathways and intermediates in the biosynthesis of natural products. The instrumental specifications have been chosen to provide ionization of a broad range of sample types, from nonpolar organic intermediates to highly-charged water-soluble molecules of molecular masses up to ~2000 and small polypeptides of larger MW yet be amenable to walk-up usage in a multi-user environment.) PUBLIC HEALTH RELEVANCE: Research on drug molecules is highly dependent upon high-resolution mass spectrometry for accurate measurement of the masses of molecules. The proposed instrument will expedite research in discovery of new therapies for cancer and infectious from marine organisms and development of diagnostics by a collective group over 60 associated researchers.